What Are Monoclonal Antibodies and How Do They Treat CLL?

Published on
March 2, 2016

Topics include:
Treatment and Understanding

What are monoclonal antibodies, and why are they
important for CLL patients? From MD
Anderson Cancer Center, CLL experts Dr. Zeev Estrov and Dr. Michael Keating describe
the function and properties of antibodies.
As Dr. Keating says, “Antibodies are key elements in everything we do in
CLL, because eventually most patients will develop significantly low levels of
the normal gamma globulins."

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Andrew Schorr:

So first of all, Dr. Estrov, what is an
antibody? And these letters and numbers,
what are we talking about?

Dr. Estrov:

Okay. So
in simple words, cells express on the surface different proteins. An antibody is something that the body makes
that binds to this protein and affects the cell. The protein that is expressed by the cell is
an antigen. And the protein that binds
to whatever is expressed on the cell is an antibody. Some of the antibodies we can generate them
in the lab, and they destroyCLL
cells.

And there are several of them, and their numbers
keep increasing. Which kind of proteins
are we going to go after? The number is
increasing. And I think that the first
proof of principle came from the work of J. Levey in Stanford University who
discovered that anti-CD-20 antibodies, CD-20 that expressed on the surface of
several cells like lymphoma cells or CLL cells can destroy the cells.

Let me just mention—Andrew may not like me for
expanding a little bit. When I learned—and
I used to teach—CLL was the easiest disease to teach. It’s an expansion of mature-looking
lymphocytes that are not now plastic; they’re not functional. We don’t have a treatment. All we have is cloanbatril that will control
the counts. That’s it.

Today, 40 percent of the patients who have CLL
with mutated immunoglobulin and heavy changing are cured with the FCR
regimen. So this is what Dr. Keating has
developed in MD Anderson. This is the
standard of care for these patients worldwide.
And it’s a big achievement. It’s
a disease that could not be cured. And
at least for a subset of patients, CLL can be cured.

This is a paradigm shift. And we will keep working on it. We will cure CLL.

Andrew
Schorr:

So just to help you understand a little bit, so
the monoclonal antibodies, like I had rituximab (Rituxan), some other people
have had it here, too, around the world.
Jeff had a different one, ofatumumab or Arzerra that’s on there. These are like cruise missiles, homing in, as
he said, onsome signal, some little
antenna on the surface of the cell. So
the cruise missile says: oh, there’s the signal; boom, trying to kill the
cell. Now the problem is, it can kill
healthy cells, right, Dr. Keating? So
it’s pretty selective but not totally selective. But adding that to FC made a huge difference.

Dr. Keating:

I think one of the things we have to realizeis that some of you around here are
receiving gamma globulin replacement IVIG.
And that’s because your natural antibody level is low. So every time we get attacked by a virus or a
bacteria or a fungus, we make these antibodies.
And as Dr. Estrov said, the antibodies attach to an antigen. So the viruses and bacteria have different
antigens in human cells. So you make an
antibody against them, and they attach to the virus. And they attach to the
bacteria, and they help the body kill them.
And they’re little Y-shaped things with a couple of attachment
molecules.

The way that these antibodies were developed was
they took leukemic cells and lymphoma cells and injected them into rats and
mice, and found out that some of the rats and mice would make antibodies which
would attack leukemic human cells and human lymphoma cells. And that led to the development of the
drug. So that all of these have somewhat
different activities. Rituxan and
ofatumumab and inotuzumab are all different ways that we can remodel the
antibodies so that they are a little more effective. There are some problems, however, in that
when we give these big molecules, they don’t get distributed evenly all aroundthe body.

And even these days they’re given by
infusion. The Germans have figured out
that you can actually give it subcutaneously, just a needle underneath the skin
and run it in over a few hours with a chemical that makes it diffuse out so
that you don’t have to have it intravenously.
There are ways now that you can get gamma globulin infusions instead of
going into the hospital and getting IVIG, you can be taught at home that you
can stick a needle in and do this and hook it up to a little bag of gamma
globulin and run it in yourself and then take it out yourself.

And it had to be given once a week, but now
Baxter has developed a way that you can have it done once a month rather than
going in there. So that antibodies are a
key element of everything that we do in CLL, because eventually most patients
with CLL will develop significantly low levels of the normal gamma globulins. And it’s been somewhat difficult to figure
out how to repair that trouble.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.